Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins

被引：258

作者：

Wang, Guoping

Nikolovska-Coleska, Zaneta

Yang, Chao-Yie

Wang, Renxiao

Tang, Guozhi

Guo, Jie

Shangary, Sanjeev

Qiu, Su

Gao, Wei

Yang, Dajun

Meagher, Jennifer

Stuckey, Jeanne

Krajewski, Krzysztof

Jiang, Sheng

Roller, Peter P.

Abaan, Hatice Ozel

Tomita, York

Wang, Shaomeng

机构：

[1] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Pharmacol & Med Chem, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA

[5] NCI, Lab Med Chem, NIH, Frederick, MD 21702 USA

[6] Georgetown Univ, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20057 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 21期

关键词：

D O I：

10.1021/jm060460o

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a K-i value of 290 nM and also to BclxL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and effectively induces apoptosis in a dose-dependent manner.

引用

页码：6139 / 6142

页数：4

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